Cocaine dependence has diverse adverse consequences and has proven difficult to treat. Behavioral interventions, including Community Reinforcement Model and Cognitive Behavior Therapy/Relapse Prevention have proven effective. Medications that might serve as effective adjuncts have been elusive. Recent primate self-administration data (Negus, 2002), several recent reports, and completion/analysis of a recent large clinical trial support further study of the agonist/ replacement approach. Still, target medications, dose, and duration must be further evaluated. [unreadable] [unreadable] This application proposes a large (140 S's, 35/group), long duration (6 month) rigorous blind randomized clinical trial. Sustained release d-amphetamine will be examined across dose range. of PBO, 45 mg, 60 mg, or 80 mg administered in identical capsules. Rigorous compliance measures using riboflavin, urine screens, and MEMS dispensing bottles will be applied. Consent will be followed by a 10 day period in which BZ positive urine screens must be provided and during which Intake and Evaluation will proceed. Medication run-up of 10 days will be followed by 20 weeks of stable medication. A dose reduction period and four weeks of behavior therapy alone will follow, Post treatment follow-up will be at 1 and 3 months. Intake evaluation will include standardized measures (.e.g. ASI, SCID, HAM A/D, Craving Questionnaire; HIV, EKG, TB, urine screens). There will be repeated weekly measures with thrice weekly urine screens. EKGs will be bi-weekly. Manual Driven Cognitive Behavior Therapy will be weekly. Blood samples will be obtained at regular intervals during run-up, maintenance, dose reduction and in the final three non-medication weeks. This design incorporates both major features and details in accord with NIDA's consensus review (January 2002) on optimal strategies for agonist evaluation. [unreadable] [unreadable]